Abstract:In the skin-healing field, porcine models are regarded as a useful analogue for human skin due to their numerous anatomical and physiological similarities. Despite the widespread use of porcine models in skin healing studies, the initial origin, recruitment and transition of fibroblasts to matrix-secreting contractile myofibroblasts are not well defined for this model. In this review, we discuss the merit of the pig as an animal for studying myofibroblast origin, as well as the challenges associated with asses… Show more
“…Model systems to isolate and study the skin microbiota often rely on murine models. Fundamental differences in murine skin compared to human skin include morphological and histological differences such as thickness, the density of pilosebaceous units and other appendages such as sweat glands, and even distinct pathways and cell types involved in repair processes ( 20 - 22 ). Furthermore, many S. aureus virulence factors are attenuated in mice ( 23 ).…”
The microbiota mediate multiple aspects of skin barrier function, including colonization resistance to pathogens such as
Staphylococcus aureus
. The endogenous skin microbiota limits
S. aureus
colonization via competition and direct inhibition. Novel mechanisms of colonization resistance are promising therapeutic targets for drug-resistant infections, such as those caused by methicillin-resistant
S. aureus
(MRSA). Here, we developed and characterized a swine model of topical microbiome perturbation and MRSA colonization. As in other model systems, topical antimicrobial treatment had a little discernable effect on community diversity though the overall microbial load was sensitive to multiple types of intervention, including swabbing. In parallel, we established a porcine skin culture collection and screened 7,700 isolates for MRSA inhibition. Using genomic and phenotypic criteria, we curated three isolates to investigate whether prophylactic colonization would inhibit MRSA colonization
in vivo
. The three-member consortium together, but not individually, provided protection against MRSA colonization, suggesting cooperation and/or synergy among the strains. Inhibitory isolates were represented across all major phyla of the pig skin microbiota and did not have a strong preference for inhibiting closely related species, suggesting that relatedness is not a condition of antagonism. These findings reveal the porcine skin as an underexplored reservoir of skin commensal species with the potential to prevent MRSA colonization and infection.
IMPORTANCE
The skin microbiota is protective against pathogens or opportunists such as
S. aureus
, the most common cause of skin and soft tissue infections.
S. aureus
can colonize normal skin and nasal passages, and colonization is a risk factor for infection, especially on breach of the skin barrier. Here, we established a pig model to study the competitive mechanisms of the skin microbiota and their role in preventing colonization by MRSA. This drug-resistant strain is also a livestock pathogen, and swine herds can be reservoirs of MRSA carriage. From 7,700 cultured skin isolates, we identified 37 unique species across three phyla that inhibited MRSA. A synthetic community of three inhibitory isolates provided protection together, but not individually,
in vivo
in a murine model of MRSA colonization. These findings suggest that antagonism is widespread in the pig skin microbiota, and these competitive interactions may be exploited to prevent MRSA colonization.
“…Model systems to isolate and study the skin microbiota often rely on murine models. Fundamental differences in murine skin compared to human skin include morphological and histological differences such as thickness, the density of pilosebaceous units and other appendages such as sweat glands, and even distinct pathways and cell types involved in repair processes ( 20 - 22 ). Furthermore, many S. aureus virulence factors are attenuated in mice ( 23 ).…”
The microbiota mediate multiple aspects of skin barrier function, including colonization resistance to pathogens such as
Staphylococcus aureus
. The endogenous skin microbiota limits
S. aureus
colonization via competition and direct inhibition. Novel mechanisms of colonization resistance are promising therapeutic targets for drug-resistant infections, such as those caused by methicillin-resistant
S. aureus
(MRSA). Here, we developed and characterized a swine model of topical microbiome perturbation and MRSA colonization. As in other model systems, topical antimicrobial treatment had a little discernable effect on community diversity though the overall microbial load was sensitive to multiple types of intervention, including swabbing. In parallel, we established a porcine skin culture collection and screened 7,700 isolates for MRSA inhibition. Using genomic and phenotypic criteria, we curated three isolates to investigate whether prophylactic colonization would inhibit MRSA colonization
in vivo
. The three-member consortium together, but not individually, provided protection against MRSA colonization, suggesting cooperation and/or synergy among the strains. Inhibitory isolates were represented across all major phyla of the pig skin microbiota and did not have a strong preference for inhibiting closely related species, suggesting that relatedness is not a condition of antagonism. These findings reveal the porcine skin as an underexplored reservoir of skin commensal species with the potential to prevent MRSA colonization and infection.
IMPORTANCE
The skin microbiota is protective against pathogens or opportunists such as
S. aureus
, the most common cause of skin and soft tissue infections.
S. aureus
can colonize normal skin and nasal passages, and colonization is a risk factor for infection, especially on breach of the skin barrier. Here, we established a pig model to study the competitive mechanisms of the skin microbiota and their role in preventing colonization by MRSA. This drug-resistant strain is also a livestock pathogen, and swine herds can be reservoirs of MRSA carriage. From 7,700 cultured skin isolates, we identified 37 unique species across three phyla that inhibited MRSA. A synthetic community of three inhibitory isolates provided protection together, but not individually,
in vivo
in a murine model of MRSA colonization. These findings suggest that antagonism is widespread in the pig skin microbiota, and these competitive interactions may be exploited to prevent MRSA colonization.
“…This supports the findings of previous studies indicating that the pig epidermis is more representative of the human epidermis than the mouse epidermis. [ 28 ] Figure 2D shows the classical marker genes for skin cell types, allowing comparisons across species. Marker genes in the epidermis ( KRT15+ and EPCAM+ ) and dermis ( DCN+ and COL1A1+ ) showed consistent expression patterns across all three species.…”
The dermis and epidermis, crucial structural layers of the skin, encompass appendages, hair follicles (HFs), and intricate cellular heterogeneity. However, an integrated spatiotemporal transcriptomic atlas of embryonic skin has not yet been described and would be invaluable for studying skinārelated diseases in humans. Here, singleācell and spatial transcriptomic analyses are performed on skin samples of normal and hairless fetal pigs across four developmental periods. The crossāspecies comparison of skin cells illustrated that the pig epidermis is more representative of the human epidermis than mice epidermis. Moreover, Phenomeāwide association study analysis revealed that the conserved genes between pigs and humans are strongly associated with human skinārelated diseases. In the epidermis, two lineage differentiation trajectories describe hair follicle (HF) morphogenesis and epidermal development. By comparing normal and hairless fetal pigs, it is found that the hair placode (Pc), the most characteristic initial structure in HFs, arises from progenitorālike OGN+/UCHL1+ cells. These progenitors appear earlier in development than the previously described early Pc cells and exhibit abnormal proliferation and migration during differentiation in hairless pigs. The study provides a valuable resource for inādepth insights into HF development, which may serve as a key reference atlas for studying human skin disease etiology using porcine models.
“…In the field of skin healing, the pig model is considered to be a useful analog of human skin because it has many anatomical and physiological similarities and to human wound healing, and it is a better model for studying skin regeneration. Functional judgment of dressings in pigs would make the conclusions more clinically applicable [117].…”
The inability of wounds to heal effectively through normal repair has become a burden that seriously affects socio-economic development and human health. The therapy of acute and chronic skin wounds still poses great clinical difficulty due to the lack of suitable functional wound dressings. It has been found that dressings made of polyurethane exhibit excellent and diverse biological properties, but lack the functionality of clinical needs, and most dressings are unable to dynamically adapt to microenvironmental changes during the healing process at different stages of chronic wounds. Therefore, the development of multifunctional polyurethane composite materials has become a hot topic of research. This review describes the changes in physicochemical and biological properties caused by the incorporation of different polymers and fillers into polyurethane dressings and describes their applications in wound repair and regeneration. We listed several polymers, mainly including natural-based polymers (e.g., collagen, chitosan, and hyaluronic acid), synthetic-based polymers (e.g., polyethylene glycol, polyvinyl alcohol, and polyacrylamide), and some other active ingredients (e.g., LL37 peptide, platelet lysate, and exosomes). In addition to an introduction to the design and application of polyurethane-related dressings, we discuss the conversion and use of advanced functional dressings for applications, as well as future directions for development, providing reference for the development and new applications of novel polyurethane dressings.
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